E-GEOD-10311
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA75607PRJNA75605PRJNA108537PRJNA129379PRJNA129377PRJNA129375PRJNA127367PRJNA115621PRJNA129487phs000225.v1.p1
PROVIDER: E-GEOD-10311 | ExpressionAtlas | 2015-08-27
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HOb) from bone explants render them a lucrative model for studying molecular physiology of bone turnover, discovery of novel anabolic therapeutics and mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs and no studies have been conducted to date to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks using genomewide expression profiling in resting and Bone Morphogenic Protein (BMP)-2 and Dexamethasone induced cells. Our data showed a vast number of genes and networks expressed predominantly in HObs as compared to closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (p=0.003) and included the binding proteins (IGFBP1, 2, 5) and IGF-2 and its receptor. Another HOb specific expression pattern included leptin and its receptor (p<10-8). Furthermore, after stimulating HObs with Dexamethasone or BMP-2, the expression of several interesting genes and pathways were observed where data supported the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs, a resource, which will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases. Experiment Overall Design: Human trabecular bone from the proximal femoral shaft was collected from two male patients, both undergoing total hip replacement. The bone chips were minced thoroughly and washed with PBS and cultured in three biological replicates in cell medium containing alpha-MEM supplemented with 2 mmol/l L-Glutamine, 100U/mL penicillin, 100mg/mL streptomycin, and 10% fetal bovine serum and grown at 37 degreeC with 5% CO2 until confluence. At 70-80% confluence, each replicate was trypsinized and sub-cultured in 6-well plates (100 000 cells/well) for 12 days. Prior to treatment, the cells were starved for 20h by adding complete cell medium containing 0.5% fetal bovine serum. The cells were then incubated for 2h and 24h with 10-7 M of dexamethasone and 10-4 mg/ml of rhBMP-2 with the same concentration of vehicle, respectively. Experiment Overall Design: At the two time points, the cell medium was removed and the cells were harvested stored in -70 degreeC until RNA extraction. Experiment Overall Design: RNA was isolated from the cell lysates using the RNeasy Mini Kit and Experiment Overall Design: expression studies were performed in triplicate (biological replicates) using the Affymetrix Human Genome U133 plus 2.0 Array (Affymetrix, Santa Clara, CA, USA). One microgram of RNA was reverse transcribed into cDNA and in vitro transcription was performed to generate biotin-labeled cRNA for subsequent hybridization. Hybridized target cRNA was then stained with streptavidin phycoerythrin, and arrays were scanned using a GeneArray Scanner at an excitation wavelength of 488nm.
2008-06-11 | E-GEOD-10311 | biostudies-arrayexpress
Project description:Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HOb) from bone explants render them a lucrative model for studying molecular physiology of bone turnover, discovery of novel anabolic therapeutics and mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs and no studies have been conducted to date to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks using genomewide expression profiling in resting and Bone Morphogenic Protein (BMP)-2 and Dexamethasone induced cells. Our data showed a vast number of genes and networks expressed predominantly in HObs as compared to closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (p=0.003) and included the binding proteins (IGFBP1, 2, 5) and IGF-2 and its receptor. Another HOb specific expression pattern included leptin and its receptor (p<10-8). Furthermore, after stimulating HObs with Dexamethasone or BMP-2, the expression of several interesting genes and pathways were observed where data supported the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs, a resource, which will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases. Keywords: cell type comparison
2008-02-01 | GSE10311 | GEO
Project description:Both sulfated hyaluronic acid and dexamethasone are candidates for the functionalization of bone grafts as they were shown to enhance the differentiation of osteoblasts from bone marrow stromal cells in vitro and in vivo. However, the underlying mechanisms are not fully understood. Furthermore, studies combining different approaches to assess to synergistic potentials are rare. In this study, we aim gain insights into the mode-of-action of both sulfated hyaluronic acid and dexamethasone by a comprehensive analysis of the cellular fraction, released matrix vesicles and the extracellular matrix, combining classical biochemical assays with mass spectrometry-based proteomics and further supported by novel bioinformatical computation.
2019-03-15 | PXD009434 | Pride
Project description:Identified a series of miRNAs transcriptionally regulated by vitamin D treatment within osteoblasts. Several miRNAs were validated in dose escalation experiments. Furthermore, downstream miRNA targets were appraised and found to regulate target message and protein levels. These findings were assessed in early and late passaged osteoblasts and found an age-dependent regulation of some miRNAs, while others were considered constituitiously expressed. Inhibitor studies of one key bone-related miRNA demonstrated the importance of this miRNA to regulate vitamin D-mediate osteoblastic differentiation during mineralizaition. Three independent sets of passage 8 primary human osteoblasts were either treated with vehicle (ethanol) or 1,25D3 (10nM) for 6 hours. Total RNA was collected using the miRNA Vana kit (ABI) and then quality assessed, and sent for miRNA array processesing.
2012-07-31 | E-GEOD-34144 | biostudies-arrayexpress
Project description:B-cell lymphoma 3-encoded protein (Bcl3) is an intimate and context-specific regulator of the NF-kB family of transcription factors, a ubiquitous master regulator involved in many homeostatic and inflammatory processes. NF‑kB signalling determines the fates of bone-forming osteoblasts and bone-resorbing osteoclasts. Herein we show that Bcl3 is a negative regulator of NF‑kB via control of osteoblast and osteoclast function. Mice lacking Bcl3 (Bcl3−/−) have congenitally increased bone density, long bone dwarfism, increased biomechanical strength and altered bone turnover. Bcl3−/− osteoblasts and osteoclasts have accelerated differentiation and increased activity; whereas, rescue overexpression with a Bcl3 mimetic peptide inhibits differentiation. Early-differentiating Bcl3−/− osteoblasts have altered gene transcription favouring bone formation, including perturbation of the RANKL-OPG axis. In a model of osteoarthritic aberrant mineralisation Bcl3−/− mice exhibit decreased pathological osteophyte formation. Cumulatively, these findings identify Bcl3 as a viable target for controlling NF‑kB signalling in the treatment of skeletal pathologies.
2019-01-17 | GSE125153 | GEO
Project description:Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.
2019-03-28 | GSE112318 | GEO
Project description:This a model from the article:
A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease
Bruce P Ayati, Claire M Edwards, Glenn F Webb and John P Wikswo.
Biology Direct2010 Apr 20;5(28).
20406449,
Abstract:
BACKGROUND:
Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease.
RESULTS:
Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined.
CONCLUSIONS:
The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches.
Note:
The paper describes three models 1) Zero-dimensional Bone Model without Tumou
r, 2) Zero-dimensional Bone Model with Tumour and 3) Zero-dimensional Bone Model with Tumour and Drug Treatment. This model corresponds to the Zero-dimensional Bo
ne Model with Tumour and Drug Treatment.
Typos in the publication:
Equation (4): The first term should be (β1/α1)^(g12/Γ) and not (β2/α2)^(g12/Γ)
Equation (14): The first term should be (β1/α1)^(((g12/(1+r12))/Γ) and not (β2/α2)^(((g12/(1+r12))/Γ)
Equation (13): The first term should be (β1/α1)^((1-g22+r22)/Γ) and not (β1/α1)^((1-g22-r22)/Γ)
All these corrections has been implemented in the model, with the authors agreement.
Beyond these, there are several mismatches between the equation numbers that are mentioned in for each equation and the reference that has been made to these equations in the figure legend.
2011-11-25 | BIOMD0000000403 | BioModels
Project description:A microRNA array was performed using human primary osteoblasts (hOB) obtained from trabecular bone of postmenopausal women after knee replacement due to osteoarthritis in order to determine the miRNAs expressed in these osteoblastic cells.
2015-12-21 | GSE74211 | GEO
Project description:Clinical investigations show that short-term treatment with gastric inhibitory polypeptide (GIP) acutely decreases serum markers of bone resorption and may increase bone formation. We report that the GIP receptor (GIPR) is expressed in human osteoclasts. Furthermore, GIP inhibits osteoclastogenesis, delays and inhibits bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways to impair nuclear translocation of nuclear factor of activated T cells 1 (NFATc1) and nuclear factor-κB (NFκB). Human osteoblasts also express GIPR. Although GIP improves osteoblast survival via cAMP and Akt-mediated pathways, expression of osteoblast-specific genes including RUNX2 and BGLAP and bone formation is not changed by GIP. Treatment of co-cultures of osteoclasts and osteoblasts with GIP decreased bone resorption but did not change formation. Antagonizing the GIPR with GIP(3-30)NH2 abolished the effects of GIP on osteoblasts and osteoclasts. Clinical studies are needed to determine if longer-term GIPR activation uncouples bone resorption and formation and improves bone mass
2022-10-01 | GSE201100 | GEO
Project description:This a model from the article:
A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease
Bruce P Ayati, Claire M Edwards, Glenn F Webb and John P Wikswo.
Biology Direct2010 Apr 20;5(28).
20406449,
Abstract:
BACKGROUND:
Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease.
RESULTS:
Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined.
CONCLUSIONS:
The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches.
Note:
The paper describes three models 1) Zero-dimensional Bone Model without Tumour, 2) Zero-dimensional Bone Model with Tumour and 3) Zero-dimensional Bone Model with Tumour and Drug Treatment. This model corresponds to the Zero-dimensional Bone Model with Tumour.
Typos in the publication:
Equation (4): The first term should be (β1/α1)^(g12/Γ) and not (β2/α2)^(g12/Γ)
Equation (14): The first term should be (β1/α1)^(((g12/(1+r12))/Γ) and not (β2/α2)^(((g12/(1+r12))/Γ)
Equation (13): The first term should be (β1/α1)^((1-g22+r22)/Γ) and not (β1/α1)^((1-g22-r22)/Γ)
All these corrections has been implemented in the model, with the authors agreement.
Beyond these, there are several mismatches between the equation numbers that are mentioned in for each equation and the reference that has been made to these equations in the figure legend.
2011-11-25 | BIOMD0000000402 | BioModels